Our recent efforts have applied the technologies described above to pediatric cancers, adult sarcomas, melanoma and breast cancers. We have been able to establish the potential of microarrays for the accurate diagnosis of pediatric cancers and for distinguishing estrogen receptor positive breast cancers from receptor negative tumors. Using data from laboratory models we have uncovered patterns of gene expressionrelated to important clinical properties of cancers such as estrogen sensitivity in breast cancer and metastasis in melanoma and osteosarcoma. Numerous candidate genes of potential biological importance have been identified for further investigation. To approach the problem of analyzing multiple genes we are using RNA interference technology coupled with high content screening using scanning microscopy to assess the phenotypic impact of altering the level of expression of candidate genes which are overexpressed. Candidate genes which are lost are evaluated by DNA sequencing. In this fashion, we are using the human genome sequence and the tools of genome technology to gain deeper understanding of how perturbations of genome function lead to the development of cancer.